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| 1 | SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors显示文摘Muta nt isocitrate dehydrog en ase 1(mlDH1)drives tumorigenesis via produci ng on cometabolite R-2-hydroxyglutarate(R-2-HG)across various tumor types.However,mlDHl in hibitors appear only effective in hematological tumors.The therapeutic ben efit in solid tumors remains elusive,likely due to the complex tumor microenvironment.In this study,we discover that R-2-HG produced by IDH1-mutant tumor cells is preferentially imported into vascular endothelial cells and remodels mitochondrial respiration to promote tumor angiogenesis,conferring a therapeutic vulnerability in IDH1-mutant solid tumors.Mechanistically,SLC1 Alz a Na'-depe ndent glutamate tran sporter that is prefere ntially expressed in en dothelial cells,facilitates the in flux of R-2-HG from the tumor microenvironment into the endothelial cells as well as the intracellular trafficking of R-2-HG from cytoplasm to mitochondria.R-2-HG hijacks SLC1A1 to promote mitochondrial Na^(+)/Ca^(2+)exchange,which activates the mitochondrial respiratory chain and fuels vascular en dothelial cell migratio n in tumor an giogenesis.SLC1A1 deficiency in mice abolishes mlDHl-promoted tumor an giogenesis as well as the therapeutic benefit of mlDHl in hibitor in solid tumors.Moreover,we report that HH2301,a newly discovered mlDHl inhibitor,shows promising efficacy in treating IDH1-mutant cholangiocarcinoma in preclinical models.Together,we identify a new role of SLC1A1 as a gatekeeper of R-2-HG-mediated crosstalk between IDH1-mutant tumor cells and vascular en dothelial cells,and dem on strate the therapeutic potential of mlDHl in hibitors in treating IDH1-muta nt solid tumors via disrupting R-2-HG-promoted tumor angiogenesis. | Xiaomin Wang Ziqi Chen Jun Xu Shuai Tang Nan An Lei Jiang Yixiang Zhang Shaoying Zhang Qingli Zhang Yanyan Shen Shijie Chen Xiaojing Lan Ting Wang Linhui Zhai Siyuwei Cao Siqi Guo Yingluo Liu Aiwei Bi Yuehong Chen Xiameng Gai Yichen Duan Ying Zheng Yixian Fu Yize Li Liang Yuan Linjiang Tong Kun Mo Mingcheng Wang Shu-Hai Lin Minjia Tan Cheng Luo Yi Chen Jia Liu Qiansen Zhang Leping Li Min Huang | 2022 | Cell Research2022,32,7: | 2 |
| 2 | Ambient Temperature and Years of Life Lost:A National Study in China显示文摘Although numerous studies have investigated premature deaths attributable to temperature,effects of temperature on years of life lost(YLL)remain unclear.We estimated the relationship between temperatures and YLL,and quantified the YLL per death caused by temperature in China.We collected daily meteorological and mortality data,and calculated the daily YLL values for 364 locations(2013–2017 in Yunnan,Guangdong,Hunan,Zhejiang,and Jilin provinces,and 2006–2011 in other locations)in China.A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates(YLL/100,000 population),and a multivariate meta-analysis model was used to pool location-specific associations.Then,YLL per death caused by temperatures was calculated.The temperature and YLL rates consistently showed U-shaped associations.A mean of 1.02(95%confidence interval:0.67,1.37)YLL per death was attributable to temperature.Cold temperature caused 0.98 YLL per death with most from moderate cold(0.84).The mean YLL per death was higher in those with cardiovascular diseases(1.14),males(1.15),younger age categories(1.31 in people aged 65–74 years),and in central China(1.34)than in those with respiratory diseases(0.47),females(0.87),older people(0.85 in people R75 years old),and northern China(0.64)or southern China(1.19).The mortality burden was modified by annual temperature and temperature variability,relative humidity,latitude,longitude,altitude,education attainment,and central heating use.Temperatures caused substantial YLL per death in China,which was modified by demographic and regional characteristics. | Tao Liu Chunliang Zhou Haoming Zhang Biao Huang Yanjun Xu Lifeng Lin Lijun Wang Ruying Hu Zhulin Hou Yize Xiao Junhua Li Xiaojun Xu Donghui Jin Mingfang Qin Qinglong Zhao Weiwei Gong Peng Yin Yiqing Xu Jianxiong Hu Jianpeng Xiao Weilin Zeng Xing Li Siqi Chen Lingchuan Guo Zuhua Rong Yonghui Zhang Cunrui Huang Yaodong Du Yuming Guo Shannon Rutherford Min Yu Maigeng Zhou Wenjun Ma | 2021 | The Innovation2021,2,1: | 1 |
| 3 | A direct laser-synthesized magnetic metamaterial for low-frequency wideband passive microwave absorption显示文摘Microwave absorption in radar stealth technology is faced with challenges in terms of its effectiveness in low-frequency regions.Herein,we report a new laser-based method for producing an ultrawideband metamaterial-based microwave absorber with a highly uniform sheet resistance and negative magnetic permeability at resonant frequencies,which results in a wide bandwidth in the L-to S-band.Control of the electrical sheet resistance uniformity has been achieved with less than 5%deviation at 400Ωsq^(-1)and 6%deviation at 120Ωsq^(-1),resulting in a microwave absorption coefficient between 97.2%and 97.7%within a1.56–18.3 GHz bandwidth for incident angles of 0°–40°,and there is no need for providing energy or an electrical power source during the operation.Porous N-and S-doped turbostratic graphene 2D patterns with embedded magnetic nanoparticles were produced simultaneously on a polyethylene terephthalate substrate via laser direct writing.The proposed low-frequency,wideband,wide-incident-angle,and high-electromagnetic-absorption microwave absorber can potentially be used in aviation,electromagnetic interference(EMI)suppression,and 5G applications. | Yihe Huang Yize Li Kewen Pan Yixian Fang Kai Chio Chan Xiaoyu Xiao Chao Wei Kostya S Novoselov John Gallop Ling Hao Zhu Liu Zhirun Hu Lin Li | 2023 | International Journal of Extreme Manufacturing2023,5,3: | 0 |
| 4 | Amorphous calcium magnesium phosphate nanocomposites with superior osteogenic activity for bone regeneration显示文摘The seek of bioactive materials for promoting bone regeneration is a challenging and longterm task.Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials.Herein,amorphous calcium magnesium phosphate(ACMP)nanoparticles and simvastatin(SIM)-loaded ACMP(ACMP/SIM)nanocomposites were developed via a simple co-precipitation strategy.The physiochemical property of ACMP/SIM was explored using transmission electron microscope(TEM),Fourier transform infrared spectroscopy(FTIR),powder X-ray diffraction(XRD)and highperformance liquid chromatograph(HPLC),and the role of Mg^(2+) in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure(XANES).After that,the transformation process of ACMP/SIM in simulated body fluid(SBF)was also tracked to simulate and explore the in vivo mineralization performance of materials.We find that ACMP/SIM releases ions of Ca^(2+),Mg^(2+)and PO_(4)^(3),when it is immersed in SBF at 37℃,and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite(HAP).Furthermore,ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells.For the in vivo studies,lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria.ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12weeks.The bioactive ACMP/SIM nanocomposites are promising as bone repair materials.Considering the facile preparation process and superior in vitro/vivo bioactivity,the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications. | Yingying Jiang Shuo Tan Jianping Hu Xin Chen Feng Chen Qianting Yao Zhi Zhou Xiansong Wang Zifei Zhou Yunshan Fan Junjian Liu Yize Lin Lijia Liu Shisheng He | 2021 | Regenerative Biomaterials2021,8,6: | 0 |